Planning, options necessary in treating pregnant women with psoriasis

Pregnancy can cause myriad changes in a woman’s body. For those with psoriasis or psoriatic disease, the good news is that their condition often clears during pregnancy.

However, pregnancy can exacerbate psoriasis symptoms in some, and symptoms may come back full force immediately after giving birth, necessitating an individual approach to treating the disease in each patient.

“Traditionally, we used to be taught 50% of psoriasis patients get better and 50% of psoriasis patients get worse,” Allison Truong, MD, FAAD, a board-certified dermatologist at Cedars-Sinai in Beverly Hills, California, said. “In my experience, sometimes psoriasis patients can flare for part of a trimester or for part of their pregnancy, but then in other parts of the pregnancy, they have no symptoms.”

A 2015 study published in Psoriasis: Targets and Therapy found 56% of patients with psoriasis improved, while 26.4% had worse symptoms and 17.6% experienced no change.

Hormones and Psoriasis

Research into the effect of hormones on psoriasis is lacking; however, estrogen is known to be anti-inflammatory and may account for the decline in symptoms.

“In some patients, the high estrogen state of pregnancy is helpful for psoriasis symptoms because it is anti-inflammatory, but the moment that you deliver your baby, you can have a flareup of your psoriasis because the estrogen drops precipitously,” Truong said.

Patients who had higher levels of estrogen throughout their pregnancy were found to have more of an improvement in their psoriasis, according to Jenny Murase, MD, director of Medical Consultative Dermatology at the Palo Alto Foundation Medical Group, associate clinical professor at UCSF and co-editor-in-chief of the International Journal of Women’s Dermatology.

“Estrogen is a nuclear receptor, just like several psoriasis therapies that are utilized,” she said. “The estrogen causes a shift, so the woman becomes more Th1 dominant, and there’s a decrease in her cell-mediated immunity.”

This makes the body have more of an allergic-dominant immune response.

To Treat or not to Treat?

Because many women experience remission in psoriasis symptoms during pregnancy, the question arises as to whether she should continue her existing medications and treatment plans.

“Psoriasis on average does not have a major negative impact on pregnancy, but there are some caveats to that,” Mark Lebwohl, MD, Waldman Chair of Dermatology at the Icahn School of Medicine at Mount Sinai, said. “There’s certainly nothing good about having extraordinary stress of a severe skin or joint condition during pregnancy.”

If a patient has a severe case of psoriasis, Lebwohl said he recommends they continue their treatment. However, there are some medications that cannot be used during pregnancy. The FDA previously assigned pregnancy categories to drugs based on their level of safety in pregnant women according to study data. The categories included A, B, C, D and X, from safest to extreme risk. These letter categories have since been replaced with a new labeling system; however, many practitioners continue to reference them.

Apremilast, an oral medication that is often a first choice in psoriasis treatment, has not been tested in pregnant women and was previously a category C, so it is often avoided or stopped in these patients. Cyclosporine, another category C drug, was used for severe psoriasis for decades before biologic medications, according to Lebwohl.

“There are no birth defects associated with cyclosporine. Nevertheless, it was given a C because prematurity and average birth weights were lower in infants born of mothers on cyclosporine,” he said.

Acitretin and methotrexate are also to be avoided due to miscarriage and birth defect risks.

“Acitretin is teratogenic, so it is contraindicated in this population,” Tiago Torres, MD, PhD, professor of dermatology at Instituto de Ciências Biomédicas Abel Salazar at the University of Porto in Porto, Portugal, said.

Topical medications and phototherapy are options that cause little to no harm to both the mother and the fetus, so they can be used throughout pregnancy.

“Phototherapy would be the best treatment for pregnant patients,” Torres said. “But there could be a logistic problem as it is difficult for the patient to come to the hospital for treatment three times a week.”

In addition, those receiving phototherapy must be cautious to protect their face during treatment to avoid melasma.

“The combination of ultraviolet light and the hormones of pregnancy can cause what’s been called the ‘mask of pregnancy,’ a pigmentary abnormality which can be disfiguring,” Lebwohl said. “We certainly protect our patient’s face during phototherapy, so they don’t develop that. Otherwise, it is a fairly benign treatment during pregnancy.”

Biologic Options

Most biologic medications were previously assigned to category B, meaning there were no adequate studies in pregnant women, but animal reproduction studies have not shown a risk to the fetus.

Tumor necrosis factor-alpha inhibitors such as infliximab, etanercept and adalimumab were shown to be safe during pregnancy, according to a 2016 article published in the Journal of the American Academy of Dermatology.

However, concerns regarding the immune system of the infant must be taken into consideration when it comes time for vaccines, according to Murase, who was one of the authors of the article.

“If you take a biologic medication and you look at the maternal cord blood levels, there are about 160% in the baby. So, they get a lot of this antibody right before delivery, and then the baby is immunosuppressed,” she said.

Her recommendation is that any live vaccines are put off for 6 to 9 months after birth to give the infant’s body time to rebuild its immune system.

“A lot of the studies reassure us that biologics are safe in pregnancy, but the problem is that the studies look at congenital malformation risk, which would be pretty irrelevant because there isn’t any antibody crossing in the first trimester,” Murase said. “But they don’t follow the babies for 3, 6, 9 months or a year. The studies end with the birth, and they say it’s safe in pregnancy. That’s good and that’s reassuring, but what about immunosuppression in the fetus?”

Alexa B. Kimball, MD, MPH, president and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, has written extensively on this topic and agreed with Murase’s assessment.

“Most biologics have good safety profiles for the first trimester and during breastfeeding. Some are actively transported across the placenta in late pregnancy, so they can cross the baby’s bloodstream during this time,” she said. “Studies looking at these babies in patients with other diseases haven’t uncovered issues, but it seems prudent to avoid that exposure if possible.”

IL-17 blockers such as secukinumab, ixekizumab and brodalumab and IL-23 blockers such as tildrakizumab, risankizumab and guselkumab all have high recapture rates, meaning if they are stopped and restarted later, they still have positive results, making them good options for women of childbearing age, Lebwohl said.

“IL-23 blockers often have very long remissions, and the duration of those remissions can be so long that it can literally take a patient through their pregnancy,” he said.

Breastfeeding Concerns

Concerns are similar for breastfeeding mothers as some medications can cross into breast milk.

“If the baby is breastfeeding with a mother that is using these biologics, we should be careful because some of the antibodies go to the baby,” Torres said.

Certolizumab pegol is one drug that minimally crosses into breast milk, making it a good option for breastfeeding women.

“With the exception of certolizumab pegol, the biologics do cross into breast milk,” Lebwohl said.

The small molecule biologics, while they can cross into breast milk, are not often seen as threatening to the infant, however.

Most women who had a reduction in psoriasis symptoms during pregnancy experience a flare shortly after delivery.

“We found that 66% of the time people flared and went right back to baseline immediately following the birth,” Murase said. “So, it’s important to have that biologic agent or whatever therapy you are using to treat the psoriasis ready and waiting so when they deliver, they can stave off the horrible flare.”

Risks to Pregnancy

Pregnant women with psoriasis or psoriatic arthritis have been found to have an excess risk for adverse maternal events, according to a 2021 metanalysis in Rheumatology.

These include an increased risk for caesarean delivery, preterm birth, preeclampsia, gestational diabetes and gestational hypertension.

“We have seen an association between psoriasis, especially more advanced psoriasis, and some increase in risk,” Kimball said. “Probably more important, however, are the conditions like smoking, high blood pressure and being overweight that increase risk in general and tend to occur more often in people with psoriasis.”

Risks to the fetus, however, have not been found to increase if the mother has psoriasis or psoriatic disease. A cohort study using the Psoriasis Longitudinal Assessment and Registry, published in JAMA Dermatology in 2020, found rates of stillbirths, spontaneous abortions and prematurity were similar to those of the general population.

Communication and Planning

For patients with psoriasis or psoriatic disease who are of childbearing age and planning to get pregnant or who are pregnant, communication with all their specialist providers remains important for the safety of their current or future pregnancies.

In the planning stages, an individually designed treatment plan can be crafted to continue throughout the pregnancy.

“You want to have your OB/GYN, your dermatologist and rheumatologist, and all of your caregivers on board when you’re thinking about getting pregnant,” Truong said. “As a patient, you have to be your own advocate, and hopefully your providers will work together to create the best regimen for you.”

Almost 50% of pregnancies, however, are unplanned, eliminating the opportunity for preplanned treatments. In these cases, patients and specialists should reevaluate any psoriasis treatment as soon as the pregnancy is confirmed.

Approximately 80% of pregnancies are not planned with a patient’s specialist providers looped in, according to Murase, who suggested all women of childbearing age be treated as if they could become pregnant.

“If you’re prescribing a therapy and the woman is of childbearing age, there’s an 80% chance that were she to have a pregnancy, you will not be consulted,” she said. “It’s really important that we have our patients on therapies that are safe and almost assume that they might get pregnant if they’re of childbearing age.”

• References:
• Kimball AB, et al. JAMA Dermatol. 2021;doi:10.1001/jamadermatol.2020.5595.
• Murase JE, et al. J Am Acad Dermatol. 2014;doi:10.1016/j.jaad.2013.09.010.
• Vena GA, et al. Psoriasis (Auckl). 2015;doi:10.2147/PTT.S82975.
• Xie W, et al. Rheumatology (Oxford). 2021;doi:10.1093/rheumatology/keab357.

• For more information:
• Alexa B. Kimball, MD, MPH, can be reached at 375 Longwood Ave., Suite 3B, Boston, MA 02215; email: clears@bidmc.harvard.edu.
• Mark Lebwohl, MD, can be reached at Mount Sinai, 5 E. 98th St., 5th Floor, New York, NY 10029; email: lebwohl@aol.com.
• Jenny Murase, MD, can be reached at 701 E. El Camino Real, 3rd Floor, Mountain View, CA 94040; email: jemurase@gmail.com.
• Tiago Torres, MD, PhD, can be reached at Praça de Gomes Teixeira, 4099-002 Porto, Portugal; email: torres.tiago@outlook.com.
• Allison Truong, MD, FAAD, can be reached at Cedars-Sinai Medical Group, 99 La Cienega Blvd. #202, Beverly Hills, CA 90211; email: allison.truong@cshs.org.